NCT00319878

Brief Summary

Aplastic anemia is a rare autoimmune disorder in which the bone marrow production of blood cells is greatly decreased or absent. Symptoms include fatigue, weakness, tiny reddish-purple marks on the skin, abnormal bruising, and bleeding from the gums, nose, or intestine. While some cases of aplastic anemia are caused by medications, toxic exposures, or inherited genes, most often the cause remains unknown. The purpose of this study is to determine the safety and efficacy of combining two drugs, sirolimus and cyclosporine, for treating individuals with aplastic anemia that has not responded to other treatments.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
52

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started May 2006

Typical duration for phase_1

Geographic Reach
1 country

4 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Posted

Study publicly available on registry

April 27, 2006

Completed
1 day until next milestone

First Submitted

Initial submission to the registry

April 28, 2006

Completed
3 days until next milestone

Study Start

First participant enrolled

May 1, 2006

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2009

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2009

Completed
Last Updated

October 7, 2008

Status Verified

October 1, 2008

Enrollment Period

3.2 years

First QC Date

April 28, 2006

Last Update Submit

October 6, 2008

Conditions

Anemia, Aplastic

Outcome Measures

Primary Outcomes (1)

  • Safety and tolerability of sirolimus and cyclosporine in each stratum of participants

    Measured at Month 6

Secondary Outcomes (4)

  • Response rate

    Measured at Months 3 and 6

  • Duration of hematologic response

    Measured at Month 6

  • Rate of clonal disease evolution

    Measured at Month 6

  • Survival

    Measured at Month 6

Study Arms (1)

1

EXPERIMENTAL

Participants will be treated with sirolimus and cyclosporine. In phase I, each dose cohort will initially enroll three patients. If no dose-limiting toxicity (DLT) is observed by Day 28 in any patient of a cohort, then 3 patients will be treated with the next highest sirolimus dose. If 1 out of 3 patients in any cohort experiences a DLT, then 3 more patients will be enrolled in that cohort. If no more patients have a DLT by Day 28, then sirolimus dose escalation will proceed. If one or more patients experience a DLT then that dose level will be considered to be the maximum tolerated sirolimus dose, and Phase II patients will be treated at the next lowest level. Cyclosporine will be given as a twice daily oral dose.

Drug: SirolimusDrug: Cyclosporine

Interventions

SirolimusDRUG

Oral loading dose followed by a once daily dose: * Cohort 1: Loading Dose - 1.2 mg; Daily Dose - 0.4 mg * Cohort 2: % Dose Increase - 100%; Loading Dose - 2.4 mg; Daily Dose - 0.8 mg * Cohort 3: % Dose Increase - 67%; Loading Dose - 3.9 mg; Daily Dose - 1.3 mg * Cohort 4: % Dose Increase - 50%; Loading Dose - 6.0 mg; Daily Dose - 2.0 mg

1
CyclosporineDRUG

Dose of 5 mg/kg divided as a twice daily oral dose

1

Eligibility Criteria

Age21 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosis of moderate or severe aplastic anemia with bone marrow cellularity of less than 25%
  • Falls within one of the following descriptions at the time of the original diagnosis:
  • For severe aplastic anemia, fulfills any two of the following three criteria: absolute neutrophil count less than 500/uL; absolute reticulocyte count less than 60,000/uL; and platelet count less than 20,000/uL
  • For moderate aplastic anemia, fulfills any two of the following three criteria: absolute neutrophil count less than 1200/ul; hemoglobin less than 8 g/dL with corrected reticulocyte count less than 1%; and platelet count less than 60,000/uL (Note: Participants who have progressed from moderate to severe aplastic anemia prior to study entry will be classified as having severe aplastic anemia)
  • Diagnosis of refractory aplastic anemia, as defined by a failure to achieve at least a partial response to ATG within 6 months of treatment. Individuals who had a prior response to ATG but who have relapsed and not responded to salvage ATG are eligible. Individuals with relapsed disease who are not candidates for salvage ATG because they experienced a serious or life-threatening complication prior to ATG are also eligible.
  • A Karnofsky performance status of at least 60%
  • Adequate organ function, as defined by creatine levels less than 1.5 times the upper limit normal (ULN), and liver function tests (AST, bilirubin) less than 2 times the ULN
  • Women of childbearing age must be willing to use effective contraception throughout the study

You may not qualify if:

  • Received ATG treatment less than 6 months prior to study entry
  • Candidate for related allogeneic stem cell transplantation
  • Active uncontrolled infection
  • History of myelodysplastic syndrome or bone marrow cytogenetic abnormalities
  • History of Fanconi's anemia or other congenital form of aplastic anemia
  • Treatment with an investigational agent within 1 month of study entry
  • HIV infection
  • Pregnant or breastfeeding

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

UCLA Center for Health Sciences

Los Angeles, California, 90095, United States

RECRUITING

Lee Moffitt Cancer Center

Tampa, Florida, 33606, United States

RECRUITING

Taussig Cancer Center, Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

RECRUITING

Penn State University Cancer Center

Hershey, Pennsylvania, 17033, United States

RECRUITING

Related Publications (4)

  • Maciejewski JP, Risitano AM. Aplastic anemia: management of adult patients. Hematology Am Soc Hematol Educ Program. 2005:110-7. doi: 10.1182/asheducation-2005.1.110.

    PMID: 16304367BACKGROUND

  • Young NS. Immunosuppressive treatment of acquired aplastic anemia and immune-mediated bone marrow failure syndromes. Int J Hematol. 2002 Feb;75(2):129-40. doi: 10.1007/BF02982017.

    PMID: 11939258BACKGROUND

  • Brodsky RA, Chen AR, Brodsky I, Jones RJ. High-dose cyclophosphamide as salvage therapy for severe aplastic anemia. Exp Hematol. 2004 May;32(5):435-40. doi: 10.1016/j.exphem.2004.02.002.

    PMID: 15145211BACKGROUND

  • Paquette RL. Diagnosis and management of aplastic anemia and myelodysplastic syndrome. Oncology (Williston Park). 2002 Sep;16(9 Suppl 10):153-61.

    PMID: 12380966BACKGROUND

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

SirolimusCyclosporine

Condition Hierarchy (Ancestors)

AnemiaHematologic DiseasesHemic and Lymphatic DiseasesBone Marrow Failure DisordersBone Marrow Diseases

Intervention Hierarchy (Ancestors)

MacrolidesLactonesOrganic ChemicalsCyclosporinsPeptides, CyclicMacrocyclic CompoundsPolycyclic CompoundsPeptidesAmino Acids, Peptides, and Proteins

Central Study Contacts

Lynn Tihopu

CONTACT

310-794-0738

Meenal Chalukya

CONTACT

310-825-8091

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH

Study Record Dates

First Submitted

April 28, 2006

First Posted

April 27, 2006

Study Start

May 1, 2006

Primary Completion

July 1, 2009

Study Completion

December 1, 2009

Last Updated

October 7, 2008

Record last verified: 2008-10

Locations

US(4)